RheumShorts: Pediatric Update

Action Points

Note that a case-control study found that potential nicotine exposure was not associated with juvenile idiopathic arthritis.

A small study suggested that lupus in teenagers may associate with depression, but the study was statistically underpowered.

This week several studies have focused on rheumatologic disorders among young patients -- depression and anxiety in systemic lupus erythematosus (SLE) and maternal smoking and jaw involvement in juvenile idiopathic arthritis (JIA).

Depression in Pediatric Lupus

Young patients with SLE or the related condition known as mixed connective tissue disease have a high prevalence of depression and anxiety, particularly among those who are minorities, a cross-sectional study found.

In a cohort of 50 patients whose median age was 16.5 years, 34% had symptoms of depression and/or anxiety, compared with 26% of a group of healthy controls, according to Andrea Knight, MD, of Children's Hospital of Philadelphia, and colleagues.

While this was not a significant difference in an analysis adjusted for age, race, and sex, another adjusted model found that nonwhite race significantly and independently predicted symptoms of depression (OR 5.4, 95% CI 1.1-27.2, P=0.04), the researchers reported online in Pediatric Rheumatology.

And the potential severity of the problem was highlighted by the finding that among the 10 patients who had symptoms of depression, seven reported suicidal ideation, Knight's group found.

Disease onset in pediatric lupus typically occurs during early adolescence, "a critical time in their psychosocial development of independence, self-identity, and skills necessary for successful transition to adult roles and relationships," the researchers wrote.

Depression and anxiety are known to have a negative influence on disease activity and medication adherence among adults with lupus.

Factors likely to contribute to depression and anxiety in teens with lupus are multiple and complex: "the psychological stress of dealing with a chronic illness during adolescence, inflammatory central nervous system pathology related to SLE, direct steroid CNS effects and indirect steroid-related somatic effects (e.g., appearance concern due to weight gain, acne, and striae), as well as hereditary and environmental factors," Knight and colleagues noted.

To explore the prevalence of these disorders in younger patients and the impact on healthcare utilization, the researchers recruited patients and controls, screening them for depression with the Patient Health Questionnaire and for anxiety with the Screen for Childhood Anxiety Related Disorders.

A total of 86% of the patients were female, 46% were white, 36% were African American, and 18% reported "other" ethnicity.

The most common manifestations of disease included cytopenia, arthritis, and skin rashes. More than two-thirds were taking glucocorticoids.

Symptoms of depression were present in 20% of the patients compared with 8% of controls, while symptoms of anxiety were detected in 22% and 26%, respectively.

A trend was seen for a greater prevalence of suicidal ideation among cases, and after adjustment for race, a statistically significant increase was seen (OR 5.4, 95% CI 1.02-28.3, P=0.047).

Among all the patients who had any symptoms of depression or anxiety, only 24% had any previous mental healthcare.

This lack of mental healthcare was "concerning," according to the authors. "This is of particular importance for pediatric SLE patients who are a disproportionately nonwhite group. The reason for this increased risk is unclear but may be related to known cultural stigma and socioeconomic barriers to diagnosing and managing depression in those of nonwhite race," they wrote.

The researchers also examined other healthcare utilizations for their cohort, and found that the mean number of outpatient visits per person-year was 7.9 (95% CI 6.9-9.1). The mean number of visits to a rheumatologist per person-year was 4.3 compared with 2.6 to a primary care provider.

Patients with symptoms of depression were less likely to have outpatient healthcare visits in general (IRR=0.67, 95% CI 0.46-0.96, P=0.03) and particularly primary care visits (IRR 0.38, 95% CI 0.19-0.76, P<0.001). However, there was no difference in the rate of visits to a rheumatologist for those with depression.

Because of the lack of primary care visits among these young patients with symptoms of depression, pediatric rheumatologists may need to keep their patients' psychological health in mind and address these concerns, the researchers advised.

"There is a need for increased awareness and further investigation of the barriers to mental healthcare and strategies for improving the mental health of pediatric SLE and mixed connective tissue disease patients," they stated.

Maternal Smoking and JIA

Maternal smoking during pregnancy did not increase the risk for JIA in the offspring, a case-control study found.

Contrary to expectations, fewer mothers of children with JIA smoked while pregnant (11%) compared with control mothers (17%), for an odds ratio of JIA of 0.71 (95% CI 0.58-0.87) in children of mothers who smoked, according to Susan Shenoi, MBBS, and colleagues from the University of Washington in Seattle.

There also was no association according to timing, with odds ratios of 2.05 (95% CI 0.77-5.50) for smoking prior to pregnancy only and 0.84 (95% CI 0.39-1.80) for tobacco use in any of the trimesters, the researchers reported online in Arthritis Care and Research.

A more prominent inverse association with smoking was seen for female offspring (OR 0.69, 95% CI 0.54-0.89).

Odds ratios for most maternal characteristics, including age, marital status, and prenatal care, were below 1, supporting an inverse association.

Exceptions to this, however, were seen for children of African-American mothers (OR 1.02, 95% CI 0.27-3.85), and for those with Medicaid billing for the birth hospitalization (OR 1.07, 95% CI 0.79-1.44).

For the subtypes of JIA, the lowest odds ratios were for oligoarticular, at 0.59 (95% CI 0.41-0.85) and extended oligoarticular, at 0.19 (95% CI 0.04-0.76).

"If such an inverse risk does indeed exist, it may be restricted to children with oligoarticular and extended oligoarticular JIA," the researchers noted.

The overall lack of an association was unexpected, in light of extensive evidence that smoking is a strong risk factor for rheumatoid arthritis in adults.

It's possible that JIA and rheumatoid arthritis have different environmental triggers, according to the researchers. Smoking has been noted to have inverse effects on some other inflammatory diseases such as ulcerative colitis, possibly through anti-inflammatory and immunosuppressive mechanisms involving nicotine.

"However, the negative associations we observed are not necessarily strong evidence of an inverse relationship, given the presence of other possible explanations," Shenoi and colleagues wrote.

"Residual confounding due to socioeconomic status may have resulted in the negative associations we observed overall and for some JIA categories. The lack of an inverse relationship among children whose mothers had Medicaid insurance at the time of delivery supports this premise," they stated.

Potential limitations of this analysis included the possibility of under-reporting of smoking and the researchers' inability to evaluate the effects of postnatal smoking or other passive smoke exposure.

Arthritis of the temporomandibular joint (TMJ) is a common but underappreciated feature of JIA that can be asymptomatic, but if detected early with MRI, treatment can be instituted and structural abnormalities possibly prevented, Swiss researchers reported.

Among a cohort of 111 patients with JIA who underwent MRI, active arthritis of the TMJ was found in 82%, yet clinical suspicion had been aroused only in 29%, according to Rotraud K. Saurenmann, MD, of University Children's Hospital in Zurich, and colleagues.

Early detection with MRI provoked changes in treatment in 62% of the cohort, the researchers reported online in Pediatric Rheumatology.

Involvement of the TMJ can occur in all subtypes of JIA, with rates of 17% to 87% having been reported, and it can be the initial affected joint, or even the only one. But the diagnosis is often delayed, and the result can be chronic inflammation of the joint.

"Mandibular dysfunction and alterations in facioskeletal morphology such as micrognathia, retrognathism, and mandibular asymmetry may be the consequences," the researchers wrote.

And by the time these abnormalities become clinically apparent, permanent damage to the chondyles may be present.

The only way to diagnose TMJ arthritis in children is with MRI, which is not always available, is costly, and parents may be unwilling to agree to sedation of the child if needed.

To examine the potential benefits of MRI in these children, Saurenmann and colleagues identified 147 patients with JIA who were enrolled in their referral center's database between 2007 and 2010. A total of 111 of these patients had undergone MRI and were included in the analysis.

Those who had TMJ arthritis detected were younger (P=0.04), more often had positive antinuclear antibodies (75%, P=0.04), and had the polyarticular or oligoarticular extended subtypes (25% and 16%, respectively). They also were significantly less likely to have the enthesitis-related subtype (P=0.012).

A total of 61 of the patients required sedation for the MRI, mostly those who were younger than 6 years of age.

Of these, 72% were given TMJ steroid injections, and in 5%, a disease-modifying anti-rheumatic drug (DMARD) was begun because of the MRI findings.

Among the patients who were not sedated for the MRI, 68% had arthritis detected. Steroid injections were then given to 32% and a DMARD begun in 12%.

While the rate of treatment change after the MRI was 62% overall, in the youngest children who were sedated, the rate was higher, at 72%. Having MRI evidence of arthritis, particularly if a young child is asymptomatic and needs sedation, may aid clinicians in convincing parents to agree to further treatments as needed, the researchers noted.

"Based on the early staged MRI, we were able to diagnose a significant amount of clinically asymptomatic children with TMJ arthritis and were able to adapt the treatment with the introduction of systemic medication and/or TMJ injections at an early stage of the disease," Saurenmann and colleagues concluded.

The authors did not disclose any relevant relationships with industry.